Abstract:

Mitochondrial dysfunctions significantly contribute to the pathogenesis of Alzheimer’s disease
(AD). Here, we studied the relationship between AD and changes in the mitochondrial rates of
respiration in blood platelets, respiratory chain complexes activity, and coenzyme Q10 plasma concentrations.
In intact platelets obtained from AD patients, we observed a decrease in endogenous basal
respiration rates, a decrease in the maximal capacity of the electron transport system (ETS), and
higher respiratory rates after inhibiting complex I of the ETS. When normalized for citrate synthase activity, rotenone inhibited
respiratory rates and complex I activity was significantly altered. In permeabilized platelets, mitochondrial respiration
was completely rescued by the addition of complex I substrates. The changes in mitochondrial respiratory parameters
were not associated with the progression of AD except for the capacity of the ETS in permeabilized platelets. In AD,
complex I activity was increased, complex IV activity was decreased, and coenzyme Q10 plasma concentrations were decreased.
Our data indicate that both insufficiency in substrates entering into the oxidative phosphorylation system and
functional disturbances in the ETS complex are responsible for the decrease in respiration observed in intact platelets in
AD patients. Analyses of complex IV activity, the respiratory rates of intact platelets, and the capacity of the ETS in permeabilized
platelets may enable the characterization of mitochondrial dysfunctions in the initial stage of AD.

Abstract:Mitochondrial dysfunctions significantly contribute to the pathogenesis of Alzheimer’s disease
(AD). Here, we studied the relationship between AD and changes in the mitochondrial rates of
respiration in blood platelets, respiratory chain complexes activity, and coenzyme Q10 plasma concentrations.
In intact platelets obtained from AD patients, we observed a decrease in endogenous basal
respiration rates, a decrease in the maximal capacity of the electron transport system (ETS), and
higher respiratory rates after inhibiting complex I of the ETS. When normalized for citrate synthase activity, rotenone inhibited
respiratory rates and complex I activity was significantly altered. In permeabilized platelets, mitochondrial respiration
was completely rescued by the addition of complex I substrates. The changes in mitochondrial respiratory parameters
were not associated with the progression of AD except for the capacity of the ETS in permeabilized platelets. In AD,
complex I activity was increased, complex IV activity was decreased, and coenzyme Q10 plasma concentrations were decreased.
Our data indicate that both insufficiency in substrates entering into the oxidative phosphorylation system and
functional disturbances in the ETS complex are responsible for the decrease in respiration observed in intact platelets in
AD patients. Analyses of complex IV activity, the respiratory rates of intact platelets, and the capacity of the ETS in permeabilized
platelets may enable the characterization of mitochondrial dysfunctions in the initial stage of AD.